Flow of Presentation
What is Lipids –
Conversion of VLDL to LDL –
Fatty acid oxidation –
Oxidation of odd carbon -
Ketone Bodies –
Metabolism of Cholesterol & functions –
Cholesterol Biosynthesis –
Regulation of Cholesterol –
Degradation of Cholesterol -
Transport of Cholesterol –
• Indispensable for cell structure & function.
• Hydrophobic & non polar nature.
• Lipid: 15-20 % of body weight in human
• Triacylglycerol: 85-90 %
• Stored in Adipose Tissue & serve as energy reserve of the
• Act as an insulating material in animal.
Why should fat be the fuel reserve of the body?
• Two reason
• TG are highly concentrated form of energy, yielding 9 cal/g, in
contrast to Carbo. & protein- 4 cal/g.
• TG are non polar & hydrophobic in nature, hence stored in
pure form without any association with water. On other hand
glycogen & protein are polar. One gram of glycogen combines
with 2 g of water for storage.
Other Imp Body Lipid
• Arachidonic Acid (unsaturated fatty acid)
TRANSPORT OF LIPID
• Insoluble lipid are solubilized in association with protein to
form lipoproteins in which lipid are transported in blood
• Free lipids are undetectable in blood
• Chylomicrons, VLDL,LDL,HDL & albumin-free fatty acid are
diff lipoprotein complex.
CONVERSION OF VLDL TO LDL
IDL (intermediate density
By losing Apo-E
LDL (Low Density
Apo- E returns to HDL
• Transfer of cholesterol is facilitate by Cholesterol ester
transfer protein (CETP)
• CETP transfers cholesterol ester from HDL to VLDL or LDL
in exchange of TG (triaclyglycerol)
• Supply cholesterol to extrahepatic tissue
• It binds to specific receptor pits called known as glycoprotein
on cell membrane
• The shape of receptor pits is stabilized by protein called
• Apo B100 is responsible for the recognition of LDL receptors
DEFICIENCY OF LDL RECEPTORS
• Elevation of plasma LDL,
• Increase in plasma Cholesterol
• Caused type IIa hyperbetalipoproteinemia
• High risk of atherosclerosis
METABOILISM OF HDL
• HDL are synthesized in liver as discoidal particles
• Contains free cholesterol and phospholipids and apoproteins
• The plasma enzyme lecithin-cholesterol acyl- transferase
(LCAT) catalyses the esterification of free cholesterol present
in the extra hepatic tissues and transfer it to the HDL
• Apo-A promotes the activity of LCAT
• With addition of cholesterol HDL particles becomes spherical
• HDL particles with cholesteryl esters trapped inside, enter the
hepatocytes by a receptor mediate endocytosis.
• In the liver cholesteryl esters are degraded to cholesterol.
• Then it is utilized for the synthesis of bile acids and
lipoproteins excreted into bile.
• FUNCTION OF HDL:
1. Transport of cholesterol
2. Serves as reservoir of apoproteins
DISORDERS OF PLASMA LIPOPROTEINS
• Mainly of two types
• Primary : Due to genetic defects
• Secondary : Due to some other diseases
• Resulting in abnormal lipoprotein patterns
• Hyper & Hypo lipoproteinemias
• Increase in one or more lipoproteins either by primary or
Deficiency of LP
Low fat diet
Deficiency of LDL
Very high in in
LDL and VLDL
Abnormality in apo-E
Very high in
Low fat &
Overproduction of TG May or may not
Low fat &
• Very low lipid levels
1. Familial hypobetalipoproteinemia: Due to impairment in
synthesis of apo protein B
Decrease in lipid up to 10-50% of normal values.
This disorder is harmless and individual have healthy and long
2. Abetalipoproteinemias: Rare and due to defect in synthesis of
apo protein B
• Total absence of b-lipoproteins in plasma, but accumulated
into liver & intenstine
• Impairment in physical growth & mental retardetion
3. Familial alpha-lipoprotein deficiency (tangier disease)
• Plasma HDL is almost absent
• Increased risk of atherosclerosis
• Normal lipid level in liver is around 5%
• In certain condition lipids especially triacyl glycerisdes
accumulated excessively into liver, resulting in fatty liver
• In the normal liver kupffer cells contains lipids in droplet
form, while in fatty liver they found in entire cytoplasm of
• This causes impairment in metabolic function of liver
• It occurs due to 1. Increased synthesis of triacylglycerols 2.
Impairment in lipoprotein synthesis
FATTY ACID OXIDATION
• β-oxidation “ Oxidation of fatty acids on the β-carbon atom.”
• This results in the sequential removal of a two carbon
fragment, acetyl CoA.
• β-oxidation of fatty acids involves 3 stages:
1. Activation of f.a. occurring in the cytosol;
2. Transport of f.a. into mitochondria;
3. β-oxidation proper in the mitochondrial matrix.
Activation of fatty acids occurring in the cytosol
Transport of fatty acids into mitochondria
Carnitine transport system
β-oxidation proper in the mitochondrial matrix
• Each cycle of β-oxidation, liberating a two carbon unitAcetyl
CoA, occurs in a sequence of four reactions.
Acyl CoA dehydrogenase
Enoyl CoA hydratase
Acyl CoA + Acetyl CoA
BETA OXIDATION OF FATTY ACIDS IN PEROXISOMES
• Peroxisomes are organelles present in most
• Beta oxidation occurs in a modified form in
• Acyl coA dehydrogenes leads to the formation
of FADH2 as in beta oxidation.
REACTION IN BETA OXIDATION OF FATTY ACIDS IN
• E-FADH2 +O2------------ E-FAD+H2O2
• H2O2--------------H2O +1/2 O2
• Ketone bodies transported from liver to
• Source of energy for the peripheral tissues
such as skeletal muscle, cardiac muscle, renal
• Utilization become more when glucose is in
short supply to the tissues, as observed in
starvation and diabetes mellitus.
• Can meet 50-70% of the brain’s energy need.
Functions of cholesterol
• Structural component of cell membrane.
• Precursor for the synthesis of all other
steroids in the body.
• Essential ingredient in the structure of
• Fatty acids are transported to liver as
cholesteryl esters for oxidation.
Steps in Biosynthesis of
Synthesis of HMG Co A
Formation of Mevalonate (6c)
Production of isoprenoid units (5c)
Synthesis of squalene (30c)
Conversion of squalene to cholesterol (27c).
PRESENT BY : GULAB YADAV
• 1gm/day synthesized in adults.
• Contribution liver (50%),Intestine(15%), skin, Adrenal
Cortex, reproductive tissue
• Enzymes are present in cytosol
• Acetyl CoA is the source of Carbon
• Production of one mole of Cholesterol
18 mole of Acetyl CoA
36 moles of ATP
16 moles of NADPH
Five Stages Of Cholesterol Synthesis
Synthesis of HMG CoA
Formation of Mevalonate (6C)
Production of Isoprenoid units (5C)
Synthesis of Squalene (30C)
Conversion of Squalene to cholesterol (27C)
STEPS OF CHOLESTEROL BIOSYNTHESIS
REGULATION OF CHOLESTEROL SYNTHESIS
• Controlled by HMG CoA reductase (E.R.)
3.Inhibition by drugs
4.Inhibition by Bile acids
1. Feedback Control:
• Increase in cellular concentration of cholesterol
reduces enzyme synthesis.
• Feedback Mechanism
2. Hormonal Regulation:
• Enzymes in two interconvertible form
• Influence of hormones (glucagon &
glucocorticoids) results in formation of inactive
HMG CoA reductase, thus decrease in cholesterol
• Insulin & thyroxine increses cholesterol production
by formation of active HMG CoA reductase
3. Inhibition by drugs:
• Compactin & lovastatin inhibits enzymes and
reduces cholesterol synthesis
4. Bile acids
DEGRADATION OF CHOLESTEROL
• SYNTHESIS OF BILE ACIDS
• SYNTHESIS OF STEROID HORMONS FROM
• SYNTHESIS OF VITAMIN D
• Healthy individuals: 150-200mg/dl
• New born :less than100mg/dl,
rises to about 150mg/dl within an year.
• Women have relatively lower Plasma
Major sources of liver cholesterol and its utilizations.
Bile salts & Bile
Cholesterol lost in
Hypercholesterolemia (literally: high blood cholesterol) is the presence of
high levels of cholesterol in the blood.
It is not a disease but a metabolic derangement that can be secondary to
many diseases and can contribute to many forms of disease, most notably
is observed in many disorders like…
HYPOTHYROIDISM ( MYXOEDEMA)
CONTROL OF HYPERCHOLESTEROLEMIA
Consumption of PUFA
Avoiding high carbohydrate diet
Impact of Lifestyles
Moderate alcohol consumption
Use of Drugs
Hypocholesterolemia is the presence of abnormally low (hypo-) levels
of cholesterol in the blood (-emia).
Several genetic defects exist in the production of cholesterol from
Acetyl CoA, resulting in hypocholesteremia.
Some disorders associated with Hypocholesterolemia are :